bims-ciryme 2021-03-14 papers

Front Neurosci. 2021 ;15 639281

Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory.

Elizabeth Susan Maywood, Johanna Elizabeth Chesham, Raphaelle Winsky-Sommerer, Nicola Jane Smyllie, Michael Harvey Hastings.

Sleep is regulated by circadian and homeostatic processes. Whereas the suprachiasmatic nucleus (SCN) is viewed as the principal mediator of circadian control, the contributions of sub-ordinate local circadian clocks distributed across the brain are unknown. To test whether the SCN and local brain clocks interact to regulate sleep, we used intersectional genetics to create temporally chimeric CK1ε Tau mice, in which dopamine 1a receptor (Drd1a)-expressing cells, a powerful pacemaking sub-population of the SCN, had a cell-autonomous circadian period of 24 h whereas the rest of the SCN and the brain had intrinsic periods of 20 h. We compared these mice with non-chimeric 24 h wild-types (WT) and 20 h CK1ε Tau mutants. The periods of the SCN ex vivo and the in vivo circadian behavior of chimeric mice were 24 h, as with WT, whereas other tissues in the chimeras had ex vivo periods of 20 h, as did all tissues from Tau mice. Nevertheless, the chimeric SCN imposed its 24 h period on the circadian patterning of sleep. When compared to 24 h WT and 20 h Tau mice, however, the sleep/wake cycle of chimeric mice under free-running conditions was disrupted, with more fragmented sleep and an increased number of short NREMS and REMS episodes. Even though the chimeras could entrain to 20 h light:dark cycles, the onset of activity and wakefulness was delayed, suggesting that SCN Drd1a-Cre cells regulate the sleep/wake transition. Chimeric mice also displayed a blunted homeostatic response to 6 h sleep deprivation (SD) with an impaired ability to recover lost sleep. Furthermore, sleep-dependent memory was compromised in chimeras, which performed significantly worse than 24 h WT and 20 h Tau mice. These results demonstrate a central role for the circadian clocks of SCN Drd1a cells in circadian sleep regulation, but they also indicate a role for extra-SCN clocks. In circumstances where the SCN and sub-ordinate local clocks are temporally mis-aligned, the SCN can maintain overall circadian control, but sleep consolidation and recovery from SD are compromised. The importance of temporal alignment between SCN and extra-SCN clocks for maintaining vigilance state, restorative sleep and memory may have relevance to circadian misalignment in humans, with environmental (e.g., shift work) causes.

Keywords: NREM sleep; REM sleep; circadian misalignment; electroencephalogram; suprachiasmatic nucleus

DOI: https://doi.org/10.3389/fnins.2021.639281

J Hypertens. 2021 Mar 11.

Light therapy improves diurnal blood pressure control in night shift workers via reduction of catecholamines: the EuRhythDia study.

Juliane Hannemann, Anika Laing, Benita Middleton, Jonathan Cridland, Bart Staels, Nikolaus Marx, Peter J Grant, Massimo Federici, Tarja Stenberg, Debra J Skene, Rainer Böger.

OBJECTIVES: Night shift work is associated with high rates of hypertension and cardiometabolic disease, which are linked to disrupted circadian rhythms. We hypothesized that timed light therapy might improve disrupted circadian rhythms and stabilize diurnal control of blood pressure and glucose in night shift workers.
METHODS: We randomized 24 rotating night shift workers (mean age, 36 ± 13 years, 7 men) who had spent a median of 6 years on rotating night shifts (median, six night shifts per month) to 12 weeks of light therapy or no intervention and compared them with 12 daytime workers (37 ± 11 years, 6 men). We measured oral glucose tolerance (OGTT), 24-h blood pressure and arterial stiffness, and the circadian profiles of melatonin, cortisol, metanephrine and nor-metanephrine at baseline, after 12 weeks of intervention, and 12 weeks after the end of intervention.
RESULTS: At baseline, fewer night shift workers showed dipper status as compared with daytime workers (29 vs. 58%; P < 0.001). After 12 weeks of light therapy, there was a highly significant increase in the proportion of dippers (to 58%; P < 0.0001). We also observed a significant decrease in serum glucose during OGTT in the light therapy group (-22%; P < 0.05) with no change in serum insulin. Whilst circadian profiles of melatonin and cortisol were unchanged, plasma metanephrine and nor-metanephrine levels were significantly reduced in the light therapy group (P < 0.01).
CONCLUSION: Timed light therapy improves diurnal blood pressure control and glucose tolerance in rotating night shift workers. This effect is unrelated to melatonin and cortisol but is paralleled by reduced catecholamine levels.

DOI: https://doi.org/10.1097/HJH.0000000000002848

Cell Mol Life Sci. 2021 Mar 08.

The circadian clock and metabolic homeostasis: entangled networks.

Leonardo Vinícius Monteiro de Assis, Henrik Oster.

The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.

Keywords: Circadian rhythms; Clock genes; Energy metabolism; SCN; Tissue clocks

DOI: https://doi.org/10.1007/s00018-021-03800-2

Mol Metab. 2021 Mar 03. pii: S2212-8778(21)00042-9. [Epub ahead of print] 101202

Brown adipocyte-specific knockout of Bmal1 causes mild but significant impairment of thermogenesis in mice.

Nazmul Hasan, Naoto Nagata, Jun-Ichi Morishige, Md Tarikul Islam, Zheng Jing, Ken-Ichi Harada, Mieda Michihiro, Masanori Ono, Hiroshi Fujiwara, Takiko Daikoku, Tomoko Fujiwara, Yoshiko Maida, Tsuguhito Ota, Shigeki Shimba, Shuichi Kaneko, Akio Fujimura, Hitoshi Ando.

OBJECTIVE: The impairment of circadian clocks is a cause of obesity, but the pathophysiological role of the circadian clock in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure.
METHODS: The mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed.
RESULTS: BA-Bmal1 KO mice maintained normal core body temperature by increasing shivering and locomotor activity, despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT, and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet.
CONCLUSIONS: These results reveal the importance of BAT clock for the maintenance of energy homeostasis and the prevention of obesity.

Keywords: Brown adipose tissue; Circadian rhythm; Clock genes; Fatty acids; Obesity; Thermogenesis

DOI: https://doi.org/10.1016/j.molmet.2021.101202